inducible regulatory t cells (itregs) in non-myeloablative sibling donor peripheral blood stem cell transplantation

Conditions: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin Lymphoma; Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Multiple Myeloma; Myelodysplastic Syndrome

Summary: this is a phase i single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory t cells (itregs) when given to adult patients undergoing non-myeloablative hla-identical sibling donor peripheral blood stem cell (pbsc) transplantation for the treatment of a high risk malignancy. up to 5 dose cohorts will be tested. once the tolerable dose is determined for itregs, enrollment will continue with an additional 10 patients using sirolimus/mycophenolate mofetil (mmf) graft-versus-host disease (gvhd) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.

co-enrollment in university of minnesota protocol mt2001-10 is required and transplantation will be according to that protocol with itregs administered the morning of day 0 followed no sooner than 4 hours later by the pbsc transplantation.

Eligibility criteria:
inclusion criteria: * 18 - 75 years of age with an hla-identical sibling donor * one of the following disease categories: * acute myelogenous leukemia - high risk cr1 (as evidenced by preceding mds, intermediate to high risk cytogenetics, ≥ 2 cycles to obtain cr, erythroblastic or megakaryocytic leukemia; cr2+. all patients must be in cr as defined by hematological recovery (anc \> 0.5x 109/l), and \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. * acute lymphocytic leukemia - high risk cr1 \[t(9;22), t (1:19), t(4;11) or other mll rearrangements\] or \>1cycle to obtain cr; cr2+. all patients must be in cr as defined by hematological recovery (anc \> 0.5x 109/l), and \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. * chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible) * non-hodgkin lymphoma or hodgkin lymphoma demonstrating chemosensitive disease * myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections * performance status: karnofsky ≥ 60% * adequate organ function within 28 days of study enrollment defined as: * liver: sgot and sgpt \< 5.0 x uln; total bilirubin \< 3 x uln * renal: serum creatinine \ 40 ml/min/1.73m2. patients with a creatinine \> 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (gfr) \> 40 ml/min/1.73m2 * albumin: \> 2.5 g/dl * cardiac: no decompensated chf or uncontrolled arrhythmia; ejection fraction \> 35% within 6 weeks prior to study enrollment * pulmonary: no o2 requirements; dlco \> 30% predicted within 6 weeks prior to study enrollment * if recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by infectious disease * sexually active females of child bearing potential and males must agree to use effective contraception for the duration of the transplant period * voluntary written consent exclusion criteria: * pregnancy or breast feeding - women of childbearing potential must have a negative pregnancy test within 28 days of study enrollment. * prior myeloablative transplant within previous 3 months of study enrollment. * evidence of hiv infection or known hiv positive serology. * active serious infection.